Tag: Antibodies

SARS-CoV-2-infection and vaccine-induced antibodies wane initially but stabilize for lasting protection

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In a recent observational study published in the journal Immunity, researchers from the United States of America investigated the longevity of antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination. They found that the humoral responses to SARS-CoV-2 infection and vaccination were long-lasting and biphasic, with an initial decline followed by stabilization after seven to nine months.

Study: SARS-CoV-2-infection- and vaccine-induced antibody responses are long lasting with an initial waning phase followed by a stabilization phase. Kateryna Kon / Shutterstock

Background

The COVID-19 pandemic, which began four years ago, prompted the rapid development of messenger RNA (mRNA) vaccines, including the BNT162b2 and mRNA-1273, helping save millions of lives. However, emerging variants of SARS-CoV-2 and the waning immunity against them pose challenges. Although mRNA-based vaccine-induced immunity is perceived to decline rapidly, this perception is based on limited data, primarily from short-term studies.

Amidst the exponential rise of SARS-CoV-2 cases in March 2020, the New York metropolitan area faced a crisis, with essential healthcare workers at a high infection risk. In response, a specific and sensitive SARS-CoV-2 enzyme-linked immunosorbent assay (ELISA) was developed, and the Protection Associated with Rapid Immunity to SARS-CoV-2 (PARIS) study was launched. This initiative tracked antibody responses, reinfection rates, and immunity factors in healthcare workers, offering vital insights into pandemic dynamics. Researchers in the present study utilized data from the PARIS study, one of the most comprehensive investigations on SARS-CoV-2 immunity longevity, and analyzed the humoral responses to SARS-CoV-2 infection and vaccination.

About the study

The PARIS study was an observational, longitudinal study conducted from April 2020 to March 2023 and enrolled 501 healthcare workers. Their mean age was 41 years, and 67% of them were female. Weekly saliva samples and bi-weekly blood samples were collected for the first two months. Nasopharyngeal/ante-near swabs were taken for respiratory symptoms or after vaccination. About 38% of participants showed baseline SARS-CoV-2-spike-binding immunoglobulin G (IgG) antibodies. A total of 93% of participants were vaccinated– 0.2% received four mRNA boosters, 2.6% had three boosters, 16.6% had two boosters, and 53.7% had one booster. Approximately 21.3% of the participants chose not to receive boosters.

The study utilized REDCap for monthly surveys on general health and SARS-CoV-2 risk, focusing on side effects after mRNA vaccinations and booster doses. Data from 228 participants were analyzed, and severity scoring was conducted, revealing reported incidence and severity trends across doses and subgroups.

Antibody titers in serum were assessed using enzyme-linked immunosorbent assay (ELISA) and optical density at 490 nm (OD₄₉₀). Statistical and quantitative analysis involved the use of the Wilcoxon test, Mann-Whitney U test, log-rank test, unweighted pair group method with arithmetic mean (UPGMA) clustering, antibody kinetic modeling including nonlinear mixed-effects (NLME) models, and demographic factor assessment in post-vaccine and post-boost models.

Results and discussion

While 38% of the participants had detectable spike-binding IgG antibodies at baseline, 62% were seronegative at the first visit. Vaccination-naïve individuals exhibited low antibody titers after the first mRNA vaccine dose, with a substantial increase after the second dose. However, individuals with pre-existing immunity reached higher and faster peak titers, maintaining over threefold higher responses after primary immunization.

Seven to nine months post-primary vaccination, antibody titers were found to achieve a steady state. Individuals with hybrid immunity maintained higher and more stable titers compared to naïve recipients, indicating the induction of long-lasting serum antibodies. Furthermore, vaccine type and age were found to affect the antibody titers in participants without hybrid immunity modestly. As per the study, the administration of booster doses elevated the threshold at which long-term serum antibody responses reached a stable state.

A total of 225 SARS-CoV-2 infections were observed in the study period, predominantly occurring after immunization, with breakthrough infections more prevalent during the Omicron wave. In individuals with vaccine-only immunity, breakthrough infections acted as equivalent boosts to antibody responses, while in those with hybrid immunity, vaccination had a more robust boosting effect compared to a second infection.

Participants with pre-existing immunity experienced more side effects after the first vaccine dose, with overall reactogenicity decreasing after subsequent doses. Booster doses induced fewer systemic side effects than the second dose in naïve participants, while those with hybrid immunity had a different pattern, showing slightly increased side effects with booster doses.

However, the study is limited by the inability to analyze mucosal immune responses, the lack of measuring neutralizing antibodies or antibodies to specific epitopes, and the lack of assessment of later variant spikes or nucleoprotein.

Conclusion

In conclusion, the present study provides evidence that antibody responses to SARS-CoV-2 mRNA vaccination exhibit a classical biphasic decay, transitioning from rapid waning to stabilization. The findings emphasize the prolonged protection provided by hybrid immunity against several variants and the potential booster-like effect of breakthrough infections in enhancing immunity.

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February 26, 2024
Omalizumab shows promise in preventing food allergy reactions in children, study finds

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A drug can make life safer for children with food allergies by preventing dangerous allergic responses to small quantities of allergy-triggering foods, according to a new study led by scientists at the Stanford School of Medicine.

The research will be published Feb. 25 in the New England Journal of Medicine. The findings suggest that regular use of the drug, omalizumab, could protect people from severe allergic responses, such as difficulty breathing, if they accidentally eat a small amount of a food they are allergic to.

I’m excited that we have a promising new treatment for multifood allergic patients. This new approach showed really great responses for many of the foods that trigger their allergies.”

Sharon Chinthrajah, MD, study’s senior author, associate professor of medicine and of pediatrics, and the acting director of the Sean N. Parker Center for Allergy and Asthma Research at Stanford Medicine

“Patients impacted by food allergies face a daily threat of life-threatening reactions due to accidental exposures,” said the study’s lead author, Robert Wood, MD, professor of pediatrics at Johns Hopkins University School of Medicine. “The study showed that omalizumab can be a layer of protection against small, accidental exposures.”

Omalizumab, which the Food and Drug Administration originally approved to treat diseases such as allergic asthma and chronic hives, binds to and inactivates the antibodies that cause many kinds of allergic disease. Based on the data collected in the new study, the FDA approved omalizumab for reducing risk of allergic reactions to foods on Feb. 16.

All study participants were severely allergic to peanuts and at least two other foods. After four months of monthly or bimonthly omalizumab injections, two-thirds of the 118 participants receiving the drug safely ate small amounts of their allergy-triggering foods. Notably, 38.4% of the study participants were younger than 6 years, an age group at high risk from accidental ingestions of allergy-triggering foods.

Allergies are common

Food allergies affect about 8% of children and 10% of adults in the United States. People with severe allergies are advised to fully avoid foods containing their allergy triggers, but common allergens such as peanuts, milk, eggs and wheat can be hidden in so many places that everyday activities such as attending parties and eating in restaurants can be challenging.

“Food allergies have significant social and psychological impacts, including the threat of allergic reactions upon accidental exposures, some of which can be life-threatening,” Chinthrajah said. Families also face economic impacts from purchasing more expensive foods to avoid allergens, she added.

In the best available treatment for food allergies, called oral immunotherapy, patients ingest tiny, gradually increasing doses of allergy-triggering foods under a doctor’s supervision to build tolerance. But oral immunotherapy itself can trigger allergic responses, desensitization to allergens can take months or years, and the process is especially lengthy for people with several food allergies, as they are usually treated for one allergy at a time. Once they are desensitized to an allergen, patients also must continue to eat the food regularly to maintain their tolerance to it -; but people often dislike foods they were long required to avoid.

“There is a real need for treatment that goes beyond vigilance and offers choices for our food allergic patients,” Chinthrajah said.

Omalizumab is an injected antibody that binds and deactivates all types of immunoglobin E, or IgE, the allergy-causing molecule in the blood and on the body’s immune cells. So far, omalizumab appears able to provide relief from multiple food allergens at once.

“We think it should have the same impact regardless of what food it is,” Chinthrajah said.

The study included 177 children with at least three food allergies each, of whom 38% were 1 to 5 years old, 37% were 6 to 11 years old, and 24% were 12 or older. Participants’ severe food allergies were verified by skin-prick testing and food challenges; they reacted to less than 100 milligrams of peanut protein and less than 300 milligrams of each other food.

Two-thirds of the participants were randomly assigned to receive omalizumab injections, and one-third received an injected placebo; the injections took place over 16 weeks. Medication doses were set based on each participant’s body weight and IgE levels, with injections given once every two or four weeks, depending on the dose needed. The participants were re-tested between weeks 16 and 20 to see how much of each allergy-triggering food they could safely tolerate.

Upon re-testing, 79 patients (66.9%) who had taken omalizumab could tolerate at least 600 mg of peanut protein, the amount in two or three peanuts, compared with only four patients (6.8%) who had the placebo. Similar proportions of patients showed improvement in their reactions to the other foods in the study.

About 80% of patients taking omalizumab were able to consume small amounts of at least one allergy-triggering food without inducing an allergenic reaction, 69% of patients could consume small amounts of two allergenic foods and 47% could eat small amounts of all three allergenic foods.

Omalizumab was safe and did not cause side effects, other than some instances of minor reactions at the site of injection. This study marks the first time its safety has been assessed in children as young as 1.

More questions

More research is needed to further understand how omalizumab could help people with food allergies, the researchers said.

“We have a lot of unanswered questions: How long do patients need to take this drug? Have we permanently changed the immune system? What factors predict which people will have the strongest response?” Chinthrajah said. “We don’t know yet.”

The team is planning studies to answer these questions and others, such as finding what type of monitoring would be needed to determine when a patient gains meaningful tolerance to an allergy-triggering food.

Many patients who have food allergies also experience other allergic conditions treated by omalizumab, Chinthrajah noted, such as asthma, allergic rhinitis (hay fever and allergies to environmental triggers such as mold, dogs or cats, or dust mites) or eczema. “One drug that could improve all of their allergic conditions is exactly what we’re hoping for,” she said.

The drug could be especially helpful for young children with severe food allergies, she added, because they tend to put things in their mouths and may not understand the dangers their allergies pose, she added.

The drug could also make it safer for community physicians to treat food allergy patients, since it cannot trigger dangerous allergic reactions, as oral immunotherapy sometimes does. “This is something that our food allergy community has been waiting a long time for,” Chinthrajah said. “It’s an easy drug regimen to implement in a medical practice, and many allergists are already using this for other allergic conditions.”

The research team included scientists from the Johns Hopkins University School of Medicine, the National Institutes of Allergy and Infectious Diseases, the Icahn School of Medicine at Mount Sinai, Massachusetts General Hospital, the University of North Carolina School of Medicine, the University of Arkansas for Medical Sciences and Arkansas Children’s Hospital, Emory University School of Medicine and Children’s Healthcare of Atlanta, University of Texas Southwestern Medical Center, Perelman School of Medicine at the University of Pennsylvania, Genentech/Roche, Novartis Pharmaceuticals Corporation, and Rho, Inc.

The research was funded by the National Institute of Allergy and Infectious Diseases and the National Center for Advancing Translational Sciences, both part of the National Institutes of Health (grant numbers UM2AI130836, UM1AI130838, UL1TR003098, UM1TR004408, UM1AI130570, UM1AI130839, UM1AI130936, UM1TR004406, UL1TR002535, UM1TR004399, UL1TR001878, UM1AI130781, UL1TR002378 and UL1TR003107), and the Claudia and Steve Stange Family Fund. Genentech/Novartis provided the investigational product and monetary support to Johns Hopkins University and collaborated on the study design.

Source:

Journal reference:

Wood, R. A., et al. (2024) Omalizumab for the Treatment of Multiple Food Allergies. New England Journal of Medicine. doi.org/10.1056/NEJMoa2312382.

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February 25, 2024
Novel monoclonal antibody shows promise in targeting HER2-positive breast cancer cells

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In a step forward for breast cancer treatment, researchers at Tohoku University have developed a novel monoclonal antibody which specifically targets a certain type of breast cancer cell. Their findings, published in the International Journal of Molecular Sciences, offer a new tool for treating this disease.

Breast cancer remains a significant global health concern that afflicts millions of people each year. The HER2-positive subtype of breast cancer is one of the most aggressive and challenging to treat. Approximately 20% of breast cancer cases are classified as HER2-positive, meaning that there is an urgent need for therapies targeted to this specific subtype.

A research team led by Yukinari Kato rose to this challenge by developing a monoclonal antibody that precisely targets HER2-positive breast cancer cells. Monoclonal antibodies are specialized proteins engineered to recognize and bind to specific targets with exceptional precision.

HER2-positive breast cancer cells have more of the HER2 protein on their surface than healthy cells. This protein plays an important role in cell growth and division, and the excess of HER2 is one reason HER2-positive tumors are aggressive. By specifically targeting HER2-positive cells, the antibody disrupts their growth and proliferation while minimizing harm to surrounding healthy tissue.

The development of this antibody represents a significant milestone in our ongoing efforts to advance breast cancer treatment. By targeting HER2-positive breast cancer cells with precision, we can offer patients a more effective and less toxic treatment option.”

Yukinari Kato, Tohoku University

The new antibody offers a more targeted and selective approach than conventional treatments, such as chemotherapy, which can cause significant collateral damage to healthy cells. This precision not only enhances the efficacy of treatment but also reduces the incidence and severity of side effects, greatly improving the quality of life of breast cancer patients.

The project is set to move to the next phase, which will include clinical trials and regulatory approval processes. The researchers will also explore potential applications of other novel antibodies in various therapeutic areas, assessing whether they can improve outcomes for people battling other types of cancer.

The research was supported by grants from the Japan Agency for Medical Research and Development (AMED), including the “Science and Technology Platform Program for Advanced Biological Medicine” and “Basis for Supporting Innovative Drug Discovery and Life Science Research (BINDS)”.

Source:

Journal reference:

Kaneko, M. K., et al. (2024). A Cancer-Specific Monoclonal Antibody against HER2 Exerts Antitumor Activities in Human Breast Cancer Xenograft Models. International Journal of Molecular Sciences. doi.org/10.3390/ijms25031941.

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February 19, 2024
Study reveals seasonal MERS-CoV peaks in Kenyan camels and potential human transmission

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In a recent study published in the CDC’s journal Emerging Infectious Diseases, researchers estimated the incidence and potential human transmission of the Middle East respiratory syndrome coronavirus (MERS-CoV) in dromedaries (nomadic camels) in northern Kenya. They found that the incidence of MERS-CoV among these animals was biphasic, peaking in October 2022 and February 2023. Further, slaughterhouse workers in contact with the dromedaries were found to show serologic signs of exposure to MERS-CoV.

Dispatch: Biphasic MERS-CoV Incidence in Nomadic Dromedaries with Putative Transmission to Humans, Kenya, 2022–2023. Image Credit: Hamady / Shutterstock

Background

MERS-CoV is prevalent in dromedary camels in the Arabian Peninsula and Africa, with >75% seroprevalence. Zoonotic transmission to humans, mainly in the Arabian Peninsula, has resulted in >2,400 cases and >800 deaths so far. Although camel breeding is a major activity in Kenya, only three cases of MERS-CoV were identified in camel-exposed humans in 2019, suggesting regional epidemiologic differences.

MERS-CoV outbreaks in farmed dromedary camels are linked with annual camel parturition, with calves testing positive for MERS-CoV ribonucleic acid (RNA) after losing maternal antibodies. Nomadic camels in Africa, with fluctuating population densities due to seasonality and food availability, have shown correlations between high population density and MERS-CoV seropositivity in Kenya, indicating gaps in our understanding of MERS-CoV circulation.

Limited infrastructure hinders field studies on nomadic camels, but the regular transportation of these animals to slaughterhouses allows for continuous testing. Leveraging this setup, researchers in the present study conducted a year-long study at a northern Kenyan slaughterhouse hub to estimate the MERS-CoV incidence in dromedaries and their potential transmission to individuals working there.

About the study

The study was conducted at a slaughterhouse hub in Isiolo, northern Kenya. Sampling was conducted from September 2022 to September 2023. Samples were collected from 10-15 dromedary camels at a frequency of 4-5 days per week. The camels (n = 2,711) originated from various administrative wards (n=12), primarily from Laisamis and Burat.

MERS-CoV RNA detection was performed using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Confirmation was done by open reading frame (ORF) 1ab qRT-PCR or sequencing. Phylogenetic analysis was additionally performed. Randomized camel serum samples (n = 369) were tested to assess MERS-CoV immunoglobulin G (IgG) levels using ELISA (short for enzyme-linked immunosorbent assay). Optical density ratio (ODR) values were obtained. Statistical analyses were conducted to explore the associations between MERS-CoV IgG levels, RNA-positivity, seasonality, camel sex, and age.

Sero-epidemiologic investigation was conducted among slaughterhouse workers in contact with dromedaries. MERS-CoV S1 IgG reactivity was assessed using ELISA. Potential cross-reactivity with SARS-CoV-2 antibodies was excluded by comparing ELISA ODRs between MERS-CoV S1 and SARS-CoV-2 S1 assays. Neutralization tests (NT) were conducted using green fluorescent protein (GFP)–encoding vesicular stomatitis virus pseudoparticles (VSVpp) carrying MERS-CoV S protein from two clades. Testing was performed on seven serum samples at a 1:20 dilution. A plaque-reduction neutralization test (PRNT) based on MERS-CoV EMC/2012 was conducted.

Results and discussion

MERS-CoV RNA was detected in 1.3% of camels. The cumulative RNA positivity rate was found to be higher in September-October 2022 (5.0%) compared to January-March 2023 (2.3%). Incidence showed biphasic peaks in October 2022 and February 2023. Phylogenetic analysis revealed high similarity (>99.93% nucleotide identity) with MERS-CoV strains from Akaki, Ethiopia, in 2019. The sequences clustered within clade C2.2, which includes strains initially identified in Kenya in 2018, indicating three putative MERS-CoV outbreaks in Kenyan camels.

MERS-CoV IgG levels had a median ODR of 2.14, with a seroprevalence of 80.76%. IgG levels were lowest in June and highest in March. A negative association was found between MERS-CoV IgG levels and RNA positivity. RNA-positivity was found to be negatively linked to the season. Compared to female camels, male camels showed a greater probability of being RNA-positive and a lower probability of being seropositive. Older animals (>3 years) had a higher (but statistically insignificant) seropositivity rate (86%) compared to animals ≤3 years (72%).

MERS-CoV S1 IgG reactivity was detected in 14.6% of Isiolo abattoir workers. The absence of MERS-CoV S1 IgG reactivity was noted in a control cohort (n = 12) without camel exposure despite high SARS-CoV-2 S1 IgG levels (92%). Notably, one serum sample showed a VSVpp-NT 50–90% reduction of foci-forming units. Additionally, results from PRNT confirmed MERS-CoV seroconversion for the sample. None of the MERS-CoV ELISA-negative samples demonstrated neutralizing capacity in VSVpp-NT and PRNT assays.

Conclusion

In conclusion, the present study revealed a biphasic incidence of MERS-CoV in dromedary camels, potentially influenced by increased animal interactions during transport and seasonal factors. The evidence of human transmission in the study highlights the need for enhanced surveillance and preventive measures to mitigate zoonotic transmission risk. Further research is warranted to investigate the dynamics of MERS-CoV circulation and formulate strategies for potential disease control and prevention.

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February 19, 2024
Genetic mechanism shields bacterial communities from viral threats

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Like humans struggling to get through the COVID-19 pandemic, bacterial cells need social distancing to thwart viruses. But in some situations, such as inside elevators or within the candy-colored bacterial structures known as “pink berries,” staying apart just isn’t feasible.

Looking like spilled Nerds or Pop Rocks, the communal, multicellular pink berries litter the submerged surface of salt marshes in and around Woods Hole. New research conducted at the Marine Biological Laboratory (MBL) uncovers evidence that a genetic mechanism may help the berry-building bacteria -; and others like them -; protect against disease. The study, published this week in Proceedings of the National Academy of Sciences, also has implications for understanding the evolution of single-celled organisms, like bacteria, into complex multicellular ones, including humans.

It tells us about the challenges we faced back when we were little balls of cells. If you’re forming multicellular structures, you’ve got to evolve some pretty fancy immune defenses in order to stay alive.”

Lizzy Wilbanks, MBL Whitman Fellow and microbiologist at the University of California, Santa Barbara

Mysterious, mutation-generating systems

Wilbanks first encountered the pink berries as a graduate student enrolled in MBL’s Microbial Diversity course. These spherical aggregates are among the structures bacteria form when genetically similar individuals stick close together and coordinate their activity. The pink berries are populated by a species of bacteria called Thiohalocapsa PSB1, which feeds itself using sulfur and light, plus a relatively small number of other symbiotic bacteria. By working together, these cells create pockets free of oxygen, which could poison them, and acquire the weight necessary to settle safely into their ideal habitat.

Like all organisms, these cooperative microbes risk contracting viruses from their environment. Pink berries and other multicellular bacteria have a heightened need for protection, since -; like us -; they are composed of genetically similar cells packed tightly together, with no social distancing possible.

“It’s a perfect cocktail for an epidemic to blow through and wipe out everything,” Wilbanks says.

Through her collaborator Blair Paul, assistant scientist at MBL, Wilbanks learned about an unusual genetic mechanism that they found to be abundant within Thiohalocapsa. Known as diversity-generating retroelements (DGRs), this system contains sections of DNA that are transcribed into RNA and back into DNA through an error-prone process, then inserted into a target gene for mutation.

In this way, DGRs introduce lots of new genetic variation, the raw material for adaptation, into specific spots within the genomes. Scientists have found these systems in viruses, bacteria, and other microbes called archaea, yet they don’t fully understand how the microbes use them.

Wilbanks and Hugo Doré, then a postdoctoral scientist in her lab and the study’s first author, began discussing what DGRs might accomplish for Thiohalocapsa. Through their research, they learned the DGRs’ target genes include components related to those found in the immune systems of multicellular organisms, including humans, plants and even some fungi. The similarity to pieces of other organisms’ immune systems prompted the researchers to suspect the DGRs might diversify the sensor proteins Thiohalocapsa uses to defend against pathogens, analogous to the antibodies in our own immune systems.

All living organisms need to detect threats they have never encountered before. Humans and other vertebrates solve this problem by shuffling and mutating genes for their sensor proteins (antibodies) to generate a diverse army of sentinels. Though recent research has shown many components of our innate immune systems evolved from bacterial ancestors, scientists have never before seen in bacteria anything like our hyper-diverse antibodies.

A widespread immunological connection

The team first looked broadly at DGRs found in bacteria and archaea, focusing on the gene responsible for turning RNA back into DNA. This method divides the DGRs from bacteria and archaea into two groups. Within the group to which Thiohalocapsa belongs, they found that 82 percent of DGRs belong to microbes that form many-celled, cooperative structures, akin to the pink berries. Even though they belonged to distantly related microbes, the DGRs’ alterations tend to affect the same kind of immune system genes as they do in Thiohalocapsa.

Examining hundreds of individual pink berries, they found that DGRs had been actively diversifying 14 of the 15 total target genes in Thiohalocapsa. The amount of the variation found for these genes changed, however, depending on the site from which the pink berries had been collected. The viruses in pools in the same marsh may vary -; perhaps driving the differences the team saw.

“The next frontier is showing what Thiohalocapsa is actually doing with its DGRs in the environment,” Wilbanks says.

In addition to offering a peek at the evolution of life, this research has practical implications. Wastewater treatment plants use multicellular bacteria to remove nutrients that can harm local ecosystems, and federal and industrial researchers are exploring a host of other applications for engineered clumps of microbes. These microbial structures face the same challenge -; viral epidemics -; as the pink berries. When engineering these microbial systems, Wilbanks says, it makes sense to mimic the DGR-based immunity of wild communal bacteria.

Source:

Marine Biological Laboratory

Journal reference:

H. Doré, H., et al. (2024). Targeted hypermutation of putative antigen sensors in multicellular bacteria. Proceedings of the National Academy of Sciences. doi.org/10.1073/pnas.2316469121.

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February 17, 2024
Maternal mRNA COVID-19 vaccination shields infants for six months

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Women who receive an mRNA-based COVID-19 vaccination or booster during pregnancy can provide their infants with strong protection against symptomatic COVID-19 infection for at least six months after birth, according to a study from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. These findings, published in Pediatrics, reinforce the importance of receiving both a COVID-19 vaccine and booster during pregnancy to ensure that infants are born with robust protection that lasts until they are old enough to be vaccinated.

COVID-19 is especially dangerous for newborns and young infants, and even healthy infants are vulnerable to COVID-19 and are at risk for severe disease. No COVID-19 vaccines currently are available for infants under six months old. Earlier results from the Multisite Observational Maternal and Infant COVID-19 Vaccine (MOMI-Vax) study revealed that when pregnant volunteers received both doses of an mRNA COVID-19 vaccine, antibodies induced by the vaccine could be found in their newborns’ cord blood. This suggested that the infants likely had some protection against COVID-19 when they were still too young to receive a vaccine. However, researchers at the NIAID-funded Infectious Diseases Clinical Research Consortium (IDCRC), which conducted the study, did not know how long these antibody levels would last or how well the infants would actually be protected. The research team hoped to gather this information by following the infants through their first six months of life.

In this portion of the study, researchers analyzed data from 475 infants born while their pregnant mothers were enrolled in the MOMI-Vax study. The study took place at nine sites across the United States. It included 271 infants whose mothers had received two doses of an mRNA COVID-19 vaccine during pregnancy. The remaining 204 infants in the study were born to mothers who had received both doses of an mRNA COVID-19 vaccine as well as a COVID-19 booster. To supplement data gathered during pregnancy and at birth, the infants were evaluated during at least one follow-up visit during their first six months after birth. Parents also reported whether their infants had become infected or had demonstrated COVID-19 symptoms.

Based on blood samples from the infants, the researchers found that newborns with high antibody levels at birth also had greater protection from COVID-19 infection during their first six months. While infants of mothers who received two COVID-19 vaccine doses had a robust antibody response at birth, infants whose mothers had received an additional booster dose during pregnancy had both higher levels of antibodies at birth and greater protection from COVID-19 infection at their follow-up visits.

While older children and adults should continue to follow guidance from the Centers for Disease Control and Prevention (CDC) to stay up-to-date on their COVID-19 vaccines and boosters, this study highlights how much maternal vaccination can benefit newborns too young to take advantage of the vaccine: During the course of this study, none of the infants examined required hospitalization for COVID-19. Researchers will continue to evaluate the data from the MOMI-Vax study for further insights concerning COVID-19 protection in infants.

Source:

NIH/National Institute of Allergy and Infectious Diseases

Journal reference:

Cardemil, C. V., et al. (2024). Maternal COVID-19 Vaccination and Prevention of Symptomatic Infection in Infants. Pediatrics. doi.org/10.1542/peds.2023-064252.

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February 16, 2024
Advanced melanoma survival rates improve significantly from 2013 to 2019, Dutch study finds

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In a recent study published in EClinicalMedicine, a group of researchers assessed the change in overall survival (OS) among advanced melanoma patients diagnosed between 2013 and 2021.

Study: Improving survival in advanced melanoma patients: a trend analysis from 2013 to 2021. Image Credit: Africa Studio/Shutterstock.com

Background

The outlook for advanced melanoma, encompassing unresolvable stage III and IV cases, has markedly improved due to the advent of novel treatments.

Starting with the Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) blocking antibody ipilimumab in 2012, the treatment landscape expanded to include B-Raf proto-oncogene, serine/threonine kinase (BRAF) inhibitors for patients with BRAF-mutant melanoma in 2012, anti-Programmed Cell Death (PD)-1 antibodies in 2015, and combinations of BRAF inhibitors with Mitogen-Activated Protein Kinase (MEK) inhibitors and ipilimumab with nivolumab in 2016.

Recent advancements also introduced therapies such as Lymphocyte-Activation Gene 3 (LAG-3) antibodies and Tumor-Infiltrating Lymphocyte (TIL) therapy. In the Netherlands, survival rates have risen following these innovations, even outside clinical trials.

Further research is needed to understand the factors driving the recent decline in survival rates and to develop strategies to improve outcomes for advanced melanoma patients, particularly in the coronavirus disease 2019 (COVID-19) pandemic and evolving treatment modalities.

About the study

The data for the present study was sourced from the Dutch Melanoma Treatment Registry (DMTR). They involved patients aged 18 and over diagnosed with advanced melanoma from 2013 to 2021, specifically focusing on those who received systemic treatment.

These patients were categorized based on the year their melanoma was diagnosed as unresectable.

Those who progressed to unresectable disease following neoadjuvant or adjuvant treatments were included from the point they commenced treatment for their unresectable condition. Exclusions were made for patients with uveal or mucosal melanoma.

Patient demographics and tumor characteristics at the point of advanced disease diagnosis – including age, gender, performance status, lactate dehydrogenase levels (LDH) levels, melanoma location and type, thickness, ulceration presence, liver and brain metastases, number of metastatic organ sites, American Joint Committee on Cancer (AJCC) 8th edition staging, and mutation status were carefully recorded. The study also differentiated between synchronous and metachronous presentations of melanoma.

Statistical analysis was conducted using various methods to compare baseline characteristics and to estimate median survival times and the impact of the year of diagnosis on overall survival.

This involved descriptive statistics, Pearson’s chi-squared, and t-tests for categorical and continuous variables, respectively. Survival analysis was performed with the Kaplan-Meier method, and the Cox proportional hazards model was applied for multivariable analysis, considering several factors identified from previous research.

Statistical computations were performed using R software and several packages for data manipulation and analysis, ensuring a comprehensive and rigorous statistical examination of the collected data.

Study results

Between 2013 and 2021, the DMTR recorded 7,928 patients with advanced melanoma. After excluding cases of uveal and mucosal melanoma, 7,317 patients were included in the analysis.

Many of these patients received systemic treatment, increasing from 74% in 2013 to 86% in 2020 and slightly decreasing to 83% in 2021.

Out of those treated, 6,260 patients were included after further exclusions for uveal and mucosal melanoma. Among these, 428 had received neoadjuvant or adjuvant treatment before their systemic treatment for advanced melanoma.

The study observed a median follow-up of 50.9 months, with the longest follow-up for the 2013 cohort at 106.0 months and the shortest for the 2021 cohort at 14.1 months.

The median age of patients diagnosed with advanced melanoma increased over the years, and there was a noticeable rise in the number of patients with poor performance status and brain metastases. Interestingly, the prevalence of synchronous metastatic disease also increased, particularly in 2020 and 2021.

Treatment modalities evolved from BRAF inhibitors and ipilimumab monotherapy to BRAF/MEK inhibitors, anti-PD-1 antibodies, and combination therapies. The study also noted changes in the duration of these treatments over time.

The median OS for systemically treated advanced melanoma patients improved from 11.2 months in 2013 to 32.0 months in 2019.

However, a decline was observed in patients diagnosed in 2020 and 2021, with median OS dropping to 26.6 and 24.0 months, respectively, although these decreases were not statistically significant.

This trend was mirrored in the melanoma-specific survival (MSS) data, with improvements seen until 2019, followed by a decrease for the cohorts of 2020 and 2021.

Furthermore, the study found that neoadjuvant and adjuvant treatments did not significantly affect survival outcomes for advanced melanoma. Patients with synchronous metastases had shorter survival than those with metachronous metastases.

Despite treatments improving survival post-2013, a concerning trend of increased mortality risk was noted for diagnoses in 2020 and 2021, underscoring the urgency for ongoing research and treatment adaptation.

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February 14, 2024
Bone marrow plasma cells require P2RX4 to sense extracellular ATP

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Radbruch, A. et al. Competence and competition: the challenge of becoming a long-lived plasma cell. Nat. Rev. Immunol. 6, 741–750 (2006).

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